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The role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer's disease

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dc.contributor.authorCade, S.
dc.contributor.authorZhou, X.F.
dc.contributor.authorBobrovskaya, L.
dc.date.issued2022
dc.description.abstractAlzheimer’s disease is a neurodegenerative condition that is potentially mediated by synaptic dysfunction before the onset of cognitive impairments. The disease mostly affects elderly people and there is currently no therapeutic which halts its progression. One therapeutic strategy for Alzheimer’s disease is to regenerate lost synapses by targeting mechanisms involved in synaptic plasticity. This strategy has led to promising drug candidates in clinical trials, but further progress needs to be made. An unresolved problem of Alzheimer’s disease is to identify the molecular mechanisms that render the aged brain susceptible to synaptic dysfunction. Understanding this susceptibility may identify drug targets which could halt, or even reverse, the disease’s progression. Brain derived neurotrophic factor is a neurotrophin expressed in the brain previously implicated in Alzheimer’s disease due to its involvement in synaptic plasticity. Low levels of the protein increase susceptibility to the disease and post-mortem studies consistently show reductions in its expression. A desirable therapeutic approach for Alzheimer’s disease is to stimulate the expression of brain derived neurotrophic factor and potentially regenerate lost synapses. However, synthesis and secretion of the protein are regulated by complex activity-dependent mechanisms within neurons, which makes this approach challenging. Moreover, the protein is synthesised as a precursor which exerts the opposite effect of its mature form through the neurotrophin receptor p75NTR. This review will evaluate current evidence on how age-related alterations in the synthesis, processing and signalling of brain derived neurotrophic factor may increase the risk of Alzheimer’s disease.
dc.identifier.citationReviews in the Neurosciences, 2022; 33(5):515-529
dc.identifier.doi10.1515/revneuro-2021-0111
dc.identifier.issn0334-1763
dc.identifier.issn2191-0200
dc.identifier.orcidZhou, X.F. [0000-0002-8687-0175]
dc.identifier.urihttps://hdl.handle.net/11541.2/30032
dc.language.isoen
dc.publisherWalter de Gruyter
dc.relation.fundingAustralian Government Research Training Program Scholarship
dc.rightsCopyright 2022 Walter de Gruyter
dc.source.urihttps://doi.org/10.1515/revneuro-2021-0111
dc.subjectbrain ageing
dc.subjectneurodegeneration
dc.subjectsynapse loss
dc.subjectsynaptic dysfunction
dc.subjectsynaptic plasticity
dc.titleThe role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer's disease
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12249117590001831 13249108040001831 Open Access Published Version
ror.mmsid9916602949001831

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